ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Objective:To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou.Methods:The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio ( HR) values and their 95% CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results:The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD ( HR=1.42, 95% CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers ( HR=2.49, 95% CI: 1.35-4.59, interaction P<0.001). Conclusion:Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

Objective:To design and evaluate a novel arcuate multi-channel rectal endoluminal applicator to enhance dose coverage of tumors in the upper and middle rectum and reduce pressure on the rectal wall.Methods:Pelvic MRI images of 200 Chinese cases without rectal lesions in the Peking University Third Hospital from July 2022 to August 2022 were retrospectively analyzed. Based on the image data, a rectal model with general characteristics of the population and two novel hard and soft rectal endoluminal applicators were designed and fabricated. The following properties of the conventional applicators and two new applicators were compared: deformation to the model rectal wall, maximum pressure, stable pressure, D 90%, D 100%, V 100%, V 150% and V 200% of the GTV, and D 2 cm3, D 1 cm3, and D 0.1 cm3 of the organs at risk (OAR). ANOVA or Kruskal-Wallis H-test was used to compare the differences among three applicators, and Dunnett's multiple comparison test was used for pairwise comparisons. Results:The novel hard and soft rectal endoluminal applicators caused less deformation of the model rectal wall. The maximum pressure on the rectal wall was (0.606 ± 0.182) kPa and (0.481 ± 0.229) kPa for the hard arcuate applicator and soft arcuate applicator, respectively, and the stable pressure was (0.207 ± 0.137) kPa and (0.055 ± 0.097) kPa, respectively, which were significantly smaller than those of the conventional applicator ( P <0.001, <0.001; P =0.024, <0.001), and the degree of reduction was at or near 50%. Under the premise of ensuring target dose, the D 2 cm3, D 1 cm3, and D 0.1 cm3 of OAR in the treatment plan designed with the novel applicator were significantly reduced compared to the cylindrical applicator (all P<0.001). Conclusion:The novel arcuate multi-channel rectal endoluminal applicator can significantly reduce rectal wall pressure and deformation, while also reducing the dose to OAR without compromising target dose coverage, offering certain therapeutic advantages.

PURPOSE: Robot-assisted technology is a forefront of surgical innovation that improves the accuracy of total knee arthroplasty (TKA). But whether the accuracy of surgery can improve the clinical efficacy still needs further research. The purpose of this study is to perform three-dimensional (3D) analysis in the early postoperative period of patients who received robot-assisted total knee arthroplasty (RATKA), and to study the trend of changes in gait parameters after RATKA and the correlation with the early clinical efficacy. METHODS: Patients who received RATKA in the Center of Joint Surgery, the First Hospital Affiliated to Army Military Medical University from October 2020 to January 2021 were included. The imaging parameters, i.e., hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, posterior condylar angle were measured 3 months post-TKA. The 3D gait analysis and clinical efficacy by Western Ontario Mac Master University Index (WOMAC) score were performed pre-TKA, 3 and 6 months post-TKA. The differences in spatiotemporal parameters of gait, kinetic parameters, and kinematic parameters of the operated limb and the contralateral limb were compared. The correlation between gait parameters and WOMAC scores was analyzed. Paired sample t-test and Wilcoxon rank-sum test were used to analyze the difference between groups, and Spearman correlation coefficient was used to analyze the correlation. RESULTS: There were 31 patients included in this study, and the imaging indexes showed that all of them returned to normal post-TKA. The WOMAC score at 3 months post-TKA was significantly lower than that pre-TKA, and there was no significant difference between at 3 and 6 months. The 3D gait analysis results showed that the double support time of the operated limb reduced at 3 and 6 months (all p < 0.05), the maximum extension and maximum external rotation of the knee joint increased at stance phase, and the maximum flexion angle, the range of motion and the maximum external rotation increased at swing phase. Compared with the preoperative data, there were significant improvements (all p < 0.05). Compared with the contralateral knee joint, the maximum external rotation of the knee joint at swing phase was smaller than that of the contralateral side, and the maximum flexion and extension moment was greater than that of the contralateral knee. The maximum external rotation moment of the joint was greater than that of the contralateral knee joint (p < 0.05). There was a negative correlation between the single support time pre-TKA and the WOMAC score at 3 months (p = 0.017), and the single support time at 3 months was negatively correlated with the WOMAC score at 6 months (p = 0.043). The cadence at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.031). The maximum knee extension at stance phase at 6 months was negatively correlated with the WOMAC score at 6 month (p = 0.048). The maximum external rotation at stance phase at 6 months was negatively correlated with the WOMAC score at 6 months (p = 0.024). CONCLUSION The 3D gait analysis of RATKA patients is more sensitive than WOMAC score in evaluating the clinical efficacy. Trend of changes in gait parameters shows that the knee joint support, flexion and extension function, range of motion, external rotation and varus deformity moment of the patient were significantly improved at 3 months after surgery, and continued to 6 months after surgery. Compared with the contralateral knee, the gait parameters of the operated limb still has significant gaps in functionality, such as the external rotation and flexion and extension. The single support time, cadence, knee extension, and knee external rotation of the operated limb have a greater correlation with the postoperative WOMAC score. Postoperative rehabilitation exercises should be emphasized, which is of great value for improving the early efficacy of RATKA.
Humans ; Arthroplasty, Replacement, Knee ; Gait Analysis ; Robotics ; Osteoarthritis, Knee/surgery* ; Knee Joint/surgery* ; Treatment Outcome ; Range of Motion, Articular ; Biomechanical Phenomena

Objective: To investigate the surgical indications and perioperative clinical outcomes of pelvic exenteration (PE) for locally advanced, recurrent pelvic malignancies and complex pelvic fistulas. Methods: This was a descriptive study.The indications for performing PE were: (1) locally advanced, recurrent pelvic malignancy or complex pelvic fistula diagnosed preoperatively by imaging and pathological examination of a biopsy; (2)preoperative agreement by a multi-disciplinary team that non-surgical and conventional surgical treatment had failed and PE was required; and (3) findings on intraoperative exploration confirming this conclusion.Contraindications to this surgical procedure comprised cardiac and respiratory dysfunction, poor nutritional status,and mental state too poor to tolerate the procedure.Clinical data of 141 patients who met the above criteria, had undergone PE in the Sixth Affiliated Hospital of Sun Yat-sen University from January 2018 to September 2022, had complete perioperative clinical data, and had given written informed consent to the procedure were collected,and the operation,relevant perioperative variables, postoperative pathological findings (curative resection), and early postoperative complications were analyzed. Results: Of the 141 included patients, 43 (30.5%) had primary malignancies, 61 (43.3%) recurrent malignancies, 28 (19.9%) complex fistulas after radical resection of malignancies,and nine (6.4%)complex fistulas caused by benign disease. There were 79 cases (56.0%) of gastrointestinal tumors, 30 cases (21.3%) of reproductive tumors, 16 cases (11.3%) of urinary tumors, and 7 cases (5.0%) of other tumors such mesenchymal tissue tumors. Among the 104 patients with primary and recurrent malignancies, 15 patients with severe complications of pelvic perineum of advanced tumors were planned to undergo palliative PE surgery for symptom relief after preoperative assessment of multidisciplinary team; the other 89 patients were evaluated for radical PE surgery. All surgeries were successfully completed. Total PE was performed on 73 patients (51.8%),anterior PE on 22 (15.6%),and posterior PE in 46 (32.6%). The median operative time was 576 (453,679) minutes, median intraoperative blood loss 500 (200, 1 200) ml, and median hospital stay 17 (13.0,30.5)days.There were no intraoperative deaths. Of the 89 patients evaluated for radical PE surgery, the radical R0 resection was achieved in 64 (71.9%) of them, R1 resection in 23 (25.8%), and R2 resection in two (2.2%). One or more postoperative complications occurred in 85 cases (60.3%), 32 (22.7%)of which were Clavien-Dindo grade III and above.One patient (0.7%)died during the perioperative period. Conclusion: PE is a valid option for treating locally advanced or recurrent pelvic malignancies and complex pelvic fistulas.
Humans ; Pelvic Exenteration/methods* ; Pelvic Neoplasms/surgery* ; Retrospective Studies ; Neoplasm Recurrence, Local/surgery* ; Postoperative Complications

Objective:To investigate the role and molecular mechanism of death receptor 5 (DR5) in early brain injury (EBI) after subarachnoid hemorrhage (SAH), as well as the neuroprotective effect of soluble DR5 (sDR5) on SAH.Methods:Experiment 1: SD rats were randomly divided into sham-operated group ( n=6) and SAH group (SAH model was established by carotid artery puncture, n=30), and the SAH group was further subdivided into post-SAH (6 h) group, post-SAH (12 h) group, post-SAH (24 h) group, post-SAH (48 h) group and post-SAH (72 h) group ( n=6); Western blotting was used to detect the expressions of tumor necrosis factor (TNF)-α and DR5; immunofluorescent DR5 and neuronal nuclear antigen (NeuN) double staining was used to evaluate the DR5 expression in neurons. Experiment 2: SD rats were randomly divided into sham-operated group, SAH group, Trail group (injected Trail agonist dordaviprone), and Trail+sDR5 group (injected dordaviprone+sDR5, n=6); at the 24 th h of successfully constructed SAH model, the caspase family protein levels were detected by Western blotting, and Tunel staining and immunofluorescent DR5 and Caspase-3 double staining were performed. Experiment 3: SD rats were divided into sham-operated group, SAH group, Trail group and Trail+sDR5 group ( n=6); long-term motor functions, by modified Gracia score, forelimb placement experiment, rotarod test and misstep experiment, were evaluated 5, 7 and 12 d after successfully constructed SAH model; and long-term learning and memory functions were detected by water maze experiment 14, 16, 18, 20 and 21 d after successfully constructed SAH model. Results:(1) Result of Experiment 1: the expressions of TNF-α and DR5 in sham-operated group, post-SAH (6 h) group, post-SAH (12 h) group, post-SAH (24 h) group, post-SAH (48 h) group and post-SAH (72 h) group were statistically different ( F=837.992, P<0.001; F=503.942, P<0.001), and these expressions peaked 24 h after SAH; immunofluorescent DR5 and NeuN double staining showed that DR5 was located in neurons after SAH. (2) Result of Experiment 2: compared with the SAH group and Trail group, the Trail+sDR5 group had significantly decreased levels of activated caspase-8, tBid and activated caspase-3, significantly decreased numbers of Tunel positive cells and DR5 and activated caspase-3 co-marked positive cells ( P<0.05). (3) Result of Experiment 3: compared with the SAH group and Trail group, the Trail+sDR5 group had significantly increased Garcia scores, decreased failure rate in forelimb placement experiment, prolonged duration of stick rotation, and decreased foot fault rate ( P<0.05), suggesting that sDR5 could improve the long-term motor function deficit after SAH; water maze experiment showed that 21 d after SAH, compared with the SAH group and Trail group, Trail+sDR5 group had significantly increased proportion of escape time in the original platform quadrat in total escape time and increased proportion of movement path in the original platform quadrat in total movement path after platform removal ( P<0.05), suggesting that sDR5 could improve long-term learning and memory impairment after SAH. Conclusion:The sDR5 can inhibit DR5-Trail-mediated neuronal apoptosis and improve long-term neurological functional deficits after SAH.

BACKGROUND: Currently, more and more infertility couples are opting for combined acupuncture to improve success rate of in vitro fertilization (IVF). However, evidence from acupuncture for improving IVF pregnancy outcomes remains a matter of debate. OBJECTIVE: To quantitatively summarized the evidence of the efficacy of acupuncture among women undergoing IVF by means of systematic review and meta-analysis. METHODS: Four English (PubMed, Web of Science, EMBASE, and Cochrane Register of Controlled Clinical Trials) and Four Chinese databases (Wanfang Databases, Chinese National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, and SinoMed) were searched from database inception until July 2, 2023. Randomized controlled trials (RCTs) that evaluated the acupuncture's effects for women undergoing IVF were included. The subgroup analysis was conducted with respect to the age of participants, different acupuncture types, type of control, acupuncture timing, geographical origin of the study, whether or not repeated IVF failure, and acupuncture sessions. Sensitivity analyses were predefifined to explore the robustness of results. The primary outcomes were clinical pregnancy rate (CPR) and live birth rate (LBR), and the secondary outcomes were ongoing pregnancy rate and miscarriage rate. Random effects model with I² statistics were used to quantify heterogeneity. Publication bias was estimated by funnel plots and Egger's tests. RESULTS: A total of 58 eligible RCTs representing 10,968 women undergoing IVF for pregnant success were identifified. Pooled CPR and LBR showed a signifificant difference between acupuncture and control groups [69 comparisons, relative risk (RR) 1.19, 95% confifidence intervals (CI) 1.12 to 1.25, I²=0], extremely low evidence; 23 comparisons, RR 1.11, 95%CI 1.02 to 1.21, I²=14.6, low evidence, respectively). Only transcutaneous electrical acupoint stimulation showed a positive effect on both CPR (16 comparisons, RR 1.17, 95%CI 1.06 to 1.29; I²=0, moderate evidence) and LBR (9 comparisons, RR 1.20, 95%CI 1.04 to 1.37; I²=8.5, extremely low evidence). Heterogeneity across studies was found and no studies were graded as high-quality evidence. CONCLUSION Results showed that the convincing evidence levels on the associations between acupuncture and IVF pregnant outcomes were relatively low, and the varied methodological design and heterogeneity might inflfluence the fifindings. (Registration No. PROSPERO CRD42021232430).
Pregnancy ; Female ; Humans ; Live Birth ; Fertilization in Vitro/methods* ; Pregnancy Outcome ; Abortion, Spontaneous ; Acupuncture Therapy

The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.
Humans ; Ischemic Stroke ; Chemokine CXCL12 ; Acupuncture Therapy ; Mesenchymal Stem Cells ; Inflammation

A fluorescence endoscopic laser confocal microscope(FELCM) was used to direct the injection of sinomenine solid lipid nanoparticles(Sin-SLN) into the joint, and the in vitro effectiveness of Sin-SLN in the treatment of rheumatoid arthritis(RA) was evaluated. Sin-SLN was prepared with the emulsion evaporation-low temperature curing method. The Sin-SLN prepared under the optimal conditions showed the encapsulation efficiency of 64.79%±3.12%, the drug loading of 3.84%±0.28%, the average particle size of(215.27±4.21) nm, and the Zeta potential of(-32.67±0.84) mV. Moreover, the Sin-SLN demonstrated good stability after sto-rage for 30 days. The rabbit model of RA was established by the subcutaneous injection of ovalbumin and complete Freund's adjuvant. Five groups were designed, including a control group, a model group, a Sin(1.5 mg·kg~(-1)) group, a Sin-SLN(1.5 mg·kg~(-1)) group, and a dexamethasone(positive drug, 1.0 mg·kg~(-1), ig) group. The control group and the model group only received puncture treatment without drug injection. After drug administration, the local skin temperature and knee joint diameter were monitored every day. The knee joint diameter and the local skin temperature were lower in the drug administration groups than in the model group(P<0.05, P<0.01). FELCM recorded the morphological alterations of the cartilage of knee joint. The Sin-SLN group showed compact tissue structure and smooth surface of the cartilage. Enzyme-linked immunosorbent assay(ELISA) was employed to determine the serum le-vels of interleukin-1(IL-1) and tumor necrosis factor-α(TNF-α). The findings revealed that the Sin-SLN group had lower IL-1 and TNF-α levels than the model group(P<0.05, P<0.01). Hematoxylin-eosin(HE) staining was employed to reveal the pathological changes of the synovial tissue, which were significantly mitigated in the Sin-SLN group. The prepared Sin-SLN had uniform particle size and high stability. Through joint injection administration, a drug reservoir was formed. Sin-SLN effectively alleviate joint swelling and cartilage damage of rabbit, down-regulated the expression of inflammatory cytokines, and inhibited the epithelial proliferation and inflammatory cell infiltration of the synovial tissue, demonstrating the efficacy in treating RA.
Animals ; Rabbits ; Tumor Necrosis Factor-alpha ; Fluorescence ; Arthritis, Rheumatoid/drug therapy* ; Interleukin-1 ; Arthritis, Experimental/drug therapy*

Objective:To explore the effects and possible mechanisms of Tyrobp gene on neuroinflammation in Tourette's syndrome mice.Methods:Twenty C57BL/ 6J and Tyrobp knock-out male mice aged 6 weeks were randomly divided into 4 groups according to random number table method: WT+ NS group, Tyrobp -/-+ NS group, WT+ IDPN group and Tyrobp -/-+ IDPN group. Mice in WT+ IDPN group and Tyrobp -/-+ IDPN group were injected with IDPN intraperitoneally at a dose of 150 mg/kg·d, while mice in WT+ NS group and Tyrobp -/-+ NS group were injected with equal volume of normal saline, once a day for 7 days. Then stereotypical behavior of mice were evaluated. Western blot was used to detect the levels of Tyrobp, TNF-α, IL-6, IL-1β, TLR4, Myd88, p-NF-κB p65 and p-IκBα in the striatum of mice. Immunofluorescence staining was used to observe the activation of microglia. Statistical analysis was performed using GraphPad Prism 8.0 software, and t-test was used for comparison between two groups. One-way ANOVA was used to compare the means of multiple samples, and LSD test was used for further pairwise comparison. Results:The results of behavior assessment showed that there were significant differences in the motor stereotypic behavior and categorical stereotypic behavior score( F=270.9, 379.7, P<0.01), and the scores in WT+ IDPN group were higher than those in Tyrobp -/-+ IDPN group (motor stereotypic behavior: (3.23±0.26), (2.13±0.21), t=9.02, P<0.05; categorical stereotypic behavior: (45.80±4.29), (26.60±3.48), t=12.00, P<0.05). Western blot results showed that there were significant differences in the protein expression level of TNF-α, IL-6, IL-1β, TLR4, Myd88, p-NF-κB p65 and p-IκBα ( F=29.07, 23.09, 39.36, 57.6, 52.55, 15.50, 40.48, all P<0.05), the level of those in WT + IDPN group was higher than those in WT+ NS group( t=8.31, 7.37, 8.13, 11.43, 10.47, 6.05, 9.96, all P<0.05), Tyrobp -/-+ IDPN group was higher than Tyrobp -/-+ NS group ( t=3.60, 3.00, 5.84, 4.81, 3.59, 2.26, 4.68, all P<0.05), and WT + IDPN group was higher than Tyrobp -/-+ IDPN group ( t=3.97, 3.93, 4.14, 6.40, 7.63, 3.45, 3.03, all P<0.05). Immunofluorescence showed that microglial cells in the striatum region of mice in WT+ IDPN group and Tyrobp -/-+ IDPN group were enlarged and microglial cells were activated, and the activation pattern of microglial cells in WT+ IDPN group was more obvious than that in Tyrobp -/-+ IDPN group. Conclusion:Tyrobp may be involved in the pathogenesis of Tourette's syndrome by promoting neuroinflammation mediated by TLR4/Myd88/NF-κB signaling pathway.